19-3595078-TAAAAAA-TAAAA

Variant names:

• chr19-3595078-TAA-T
• rs34885751
• NM_001060.6:c.*608_*609delTT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_201636.3(TBXA2R):​c.984-4_984-3delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 468,042 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000093 (0 hom., cov: 0)
  • Exomes 𝑓: 0.032 (0 hom.)
• Consequence: TBXA2R NM_201636.3 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.623
• Publications: 3 publications found

Genes affected

TBXA2R (HGNC:11608): (thromboxane A2 receptor) This gene encodes a member of the G protein-coupled receptor family. The protein interacts with thromboxane A2 to induce platelet aggregation and regulate hemostasis. A mutation in this gene results in a bleeding disorder. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

TBXA2R Gene-Disease associations (from GenCC):

• bleeding diathesis due to thromboxane synthesis deficiency

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• bleeding disorder, platelet-type, 13, susceptibility to

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
• qualitative platelet defect

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 19-3595078-TAA-T is Benign according to our data. Variant chr19-3595078-TAA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1207313.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201636.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	NM_001060.6	MANE Select	c.*608_*609delTT		3_prime_UTR	Exon 3 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.984-4_984-3delTT		splice_region intron	N/A	NP_963998.2	P21731-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	ENST00000375190.10	TSL:1 MANE Select	c.*608_*609delTT		3_prime_UTR	Exon 3 of 3	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000589966.1	TSL:1	c.*471_*472delTT		3_prime_UTR	Exon 2 of 2	ENSP00000468145.1	K7ER80
	TBXA2R	ENST00000882306.1		c.*608_*609delTT		3_prime_UTR	Exon 3 of 3	ENSP00000552365.1

Frequencies

GnomAD3 genomes AF: 0.0000927 AC: 12 AN: 129436 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000879

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000308

Gnomad EAS AF: 0.000238

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000598

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000485

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0376 AC: 1505 AN: 40008 AF XY: 0.0375

Gnomad AFR exome AF: 0.0269

Gnomad AMR exome AF: 0.0386

Gnomad ASJ exome AF: 0.0323

Gnomad EAS exome AF: 0.0467

Gnomad FIN exome AF: 0.0485

Gnomad NFE exome AF: 0.0325

Gnomad OTH exome AF: 0.0391

GnomAD4 exome AF: 0.0319 AC: 10806 AN: 338606 Hom.: 0 AF XY: 0.0327 AC XY: 5871 AN XY: 179810

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0302 AC: 252 AN: 8334

American (AMR) AF: 0.0378 AC: 602 AN: 15930

Ashkenazi Jewish (ASJ) AF: 0.0371 AC: 316 AN: 8524

East Asian (EAS) AF: 0.0496 AC: 957 AN: 19298

South Asian (SAS) AF: 0.0375 AC: 1510 AN: 40218

European-Finnish (FIN) AF: 0.0311 AC: 450 AN: 14472

Middle Eastern (MID) AF: 0.0324 AC: 38 AN: 1172

European-Non Finnish (NFE) AF: 0.0285 AC: 6102 AN: 213894

Other (OTH) AF: 0.0345 AC: 579 AN: 16764

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000927 AC: 12 AN: 129436 Hom.: 0 Cov.: 0 AF XY: 0.000130 AC XY: 8 AN XY: 61538

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000879 AC: 3 AN: 34124

American (AMR) AF: 0.00 AC: 0 AN: 12634

Ashkenazi Jewish (ASJ) AF: 0.000308 AC: 1 AN: 3242

East Asian (EAS) AF: 0.000238 AC: 1 AN: 4208

South Asian (SAS) AF: 0.00 AC: 0 AN: 3918

European-Finnish (FIN) AF: 0.000598 AC: 4 AN: 6694

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.0000485 AC: 3 AN: 61800

Other (OTH) AF: 0.00 AC: 0 AN: 1752

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 409

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34885751; hg19: chr19-3595076;